We have established a Clinical Cancer Genetics Program which serves the patient population of the NCI as well as the National Naval Medical Center (NNMC). We are active participants in the integration of clinical cancer genetics activities across Branches, Divisions, and Institutes. We provide the critical infrastructure and resources for providing risk assessment, education, counseling and germline genetic testing for patients whose family history is suggestive of a cancer susceptibility syndrome. A multi-disciplinary team including a medical oncologist, a senior cancer genetics nurse specialist, a medical geneticist/gynecologist, and a surgical oncologist has been assembled. Additonally a CLIA-certified laboratory for microsatellite instability has been established in the laboratory of Ilan Kirsch, MD. The program has focused on breast and colorectal cancer to date because of the clinical availability of cancer predisposition genetic testing and access to potential participants which are seen within the general patient populations at NCI and NNMC. The portfolio of clinical research protocols focuses on three areas: 1) methods of education and counseling, 2) biomarker identification, and 3) intervention studies to reduce risk. In the education and counseling arena, we recently completed accrual and are analyzing the results of a clinical trial comparing different methods of counseling (group versus individual) and test result communication (phone versus in-person) in patients at high risk for carrying a germline mutation in the BRCA1 or BRCA2 genes. A cohort study of education and counseling for individuals at high risk for carrying a mutation in one of the hereditary non-polyposis colorectal cancer (HNPCC) mismatch repair genes is also being conducted in the Branch in collaboration with Don Hadley, MS, from the National Human Genome Research Institute. Patients identified from the gastroenterology clinics at NNMC who are at high risk for colorectal cancer are offered participation in a colorectal cancer chemoprevention study of the role of celecoxib to modulate rectal aberrant crypts and other biomarkers. Biological materials for laboratory investigation include colorectal biopsies from neoplastic lesions as well as normal appearing mucosa are obtained in this study. We previously have shown that cDNA gene expression can distinguish the right colon from the left colon in patients with HNPCC and plan to determine if this is true for patients at risk for sporadic cancer enrolled in this study. Additionally, we are determining if responders to celecoxib chemoprevention interventions can be distinguished from non-responders by cDNA gene expression analysis. We are evaluating the role of polymorphisms in estrogen biosynthesis and metabolism in breast cancer and mammographic density in the Susceptibility to Breast Cancer Study. Participants from three groups (breast cancer cases, high risk, and average risk controls) complete a breast cancer risk factor questionnaire, donate blood, and undergo nipple aspiration for collection of nipple fluid. Breast tissue from preneoplastic and neoplastic lesions is collected when feasible. This study provides a biological resource for biomarker investigation with our laboratory collaborators.